This retrospective, IRB-approved study analyzed placental tissue from 40 women who had COVID-19 during pregnancy to evaluate whether SARS-CoV-2 RNA persists in the placenta. The investigation used in situ hybridization to detect viral RNA in placental disk and fetal membrane, immunostaining to assess S-protein and N-protein expression, and partial viral RNA sequencing in a subset of cases. The core finding was persistent viral RNA expression localized predominantly to placental villous tissue.
Placental specimens from 40 women infected with SARS-CoV-2 at various gestational ages were examined. Viral RNA expression was assessed by in situ hybridization on sections of the placental disk and fetal membrane. Immunostaining was performed to detect S- and N-protein expression. Partial SARS-CoV-2 RNA sequencing, focusing on the RNA-dependent RNA polymerase (RdRp) region, was completed in 12 of the 29 cases that were positive for viral RNA by in situ hybridization. The study is described as retrospective and approved by an institutional review board.
SARS-CoV-2 RNA expression was detected in the placental disk in 29 of the 40 cases, with predominant localization to syncytiotrophoblasts of the villous tissue. Viral RNA was not detected in fetal membrane sections. In two placentas from infants who were COVID-positive at birth, viral RNA was also found in the villous core vessel endothelium. In those same two COVID-positive newborn placentas, corresponding S-protein and N-protein expression were present in syncytiotrophoblasts. However, overall S- and N-protein expression was undetectable in 27 of the 29 cases with positive viral RNA by in situ hybridization.
Representative histology and in situ hybridization images provided in the report illustrate typical villous architecture, the localization of syncytiotrophoblasts, and examples of positive and negative SARS-CoV-2 RNA expression across first-, second-, and third-trimester infections. Figures highlight that villous tissue frequently shows RNA signal while fetal membranes do not.
Among the 29 placentas with detectable SARS-CoV-2 RNA, maternal infection occurred across gestation: 4 in the first trimester, 7 in the second trimester, and 18 in the third trimester or at term. The maximum reported interval from maternal infection to delivery was 221 days. Of the 21 women who tested positive for COVID-19 at admission for labor and delivery, 18 (85.7%) had placental viral RNA detected. Notably, among 19 women who tested negative at admission, 11 (57.9%) nevertheless had viral RNA expression in placental villous tissue, indicating RNA persistence despite negative maternal tests at delivery.
Partial sequence of the RNA-dependent RNA polymerase (RdRp) region was identified in all 12 cases subjected to viral RNA sequencing. The authors note that the detection of partial RdRp sequences could potentially explain why S- and N-proteins were undetectable in many RNA-positive specimens, though the abstract does not provide further sequence detail, viral integrity assessments, or analysis of full genomes.
The authors conclude that these data provide compelling evidence that SARS-CoV-2 genetic material can persist in placental tissue long after maternal infection. They propose that such persistence may contribute to a sustained inflammatory environment at the maternal–fetal interface during pregnancy. The phenomenon of detecting partial RdRp sequence is offered as a possible explanation for frequent absence of detectable S- and N-protein expression in samples with RNA positivity.
The abstract reports localization patterns, frequency of RNA detection across trimester of infection, limited concordance of protein detection, and partial RdRp sequence identification. Details not reported in the abstract include clinical outcomes for mothers or neonates beyond the two COVID-positive newborns mentioned, quantitative measures of RNA signal, full sequencing results, or functional assays demonstrating infectious virus or specific inflammatory markers in the placenta.